In recent years, there has been a tendency to increase the number of patients suffering ophthalmic diseases with the progress of population aging. The progress of amblyopia by an ophthalmic disease leads to blindness in the worst case, and the patient is markedly impaired in the quality of life. Therefore, it is required to detect the disease in its early stage and take a measure to cure the disease or retard the progress thereof. Typical diseases forming a cause of halfway blindness include diabetic retinopathy, macular degeneration diseases and glaucoma, and the fundus retina is concerned with many of them. For diagnoses of these diseases, diagnoses by evaluation of visual function by inspection of visual field, and morphological evaluation of the fundus retina using a fundus camera, an optical coherence tomograph (OCT) and a scanning laser ophthalmoscope are conducted.
In a retinopathic disease, reduction of visual functions is caused by disorder of neurocytes. In recent years, it has become possible to visualize the condition of a layer structure of a reticular tissue by an OCT technique, and many new findings relating to a living body tissue of a retinal lesion have been obtained. However, a current OCT image is low in resolution, and so it has been unable to visualize the morphology of cells forming the retina.
As a visualization technique of an ocular tissue, a method of imaging and staining the ocular tissue using a staining compound has heretofore been known. For example, there is a method of visualizing a choroidal vessel and a retinal vessel using a fluorescent pigment such as indocyanine green or fluorescein (Ophthalmologic Photograph, 23, pp. 3-10(2007)). As a staining method of the cornea, a method of using rose Bengal or fluorescein is also known (EYE CONTACT LENS, 34, pages 61 to 64 (2008)).
On the other hand, as a visualization technique of intraocular tissues such as a vitreous body, retina and optic nerve, a method of administering a stain composition to a vitreous cavity mainly at surgical operation is disclosed. For example, there is a composition for staining a retinal membrane in a vitreous retina surgery (Japanese Patent No. 3469198). It is also disclosed that a transmission substance injected into the vitreous body remains in the retina (Japanese Patent Application Laid-Open No. 2007-262078). Besides, it is reported that in order to image retinal ganglion cells of a rat, a retrograde axonal transport tracer is injected into a superior colliculus of the midbrain linking to a retinal ganglion to observe it with a laser ophthalmoscope (Invest Ophthalmol Vis Sci, 47(10), p. 4198 (2006)). As described above, it has been necessary to directly administer the stain composition to the inside of an eye for visualizing the intraocular tissue.
Incidentally, a drug to act on the retina or retinal nerve tissue is administered by intravenous injection or orally. However, the quantity of the drug transferred to the retina is extremely small. On the other hand, drug administration to the vitreous cavity enables a large quantity of the drug transferred to the retinal tissue compared with the intravenous injection or oral administration. However, an advanced technique is required, and a burden on a patient is also great, and so it is extremely difficult to use it except for the case of surgery or curing, and such administration has been unable to be used for the morphological or functional evaluation of the fundus retina.